The goal is to determine what kind of molecules contribute to ionic permeability changes in nerve membranes. Ionic currents of myelinated nerve will be studied under voltage clamp conditions to determine the effect of drugs, enzymes, ions, and other modifications. Experiments will be designed to reveal the nature of voltage-dependent gating in channels; to determine the dimensions and energy barriers to ion movement inside the channel; and to test for negative surface charge in the vicinity of the channel. Model systems and theories will be explored to further define the meaning and properties of pores. BIBLIOGRAPHIC REFERENCES: Hille, B. 1975. A four barrier model of the sodium channel. Biophysical Society Abstracts, 19th Annual Meeting, 164a; Hille, B. 1975. An essential ionized acid group in sodium channels. Federation Proceedings 34:1318-1321.